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Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

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To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRB1 and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P=0.012) and *1302 (P=0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 (P=0.012) and *0609 (P=0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0609 found as common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 (P=0.025) and HLA-DQB1*0601 (P=0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection.

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CT scanning is a relatively high-dose procedure. In spite of the use of magnetic resonance imaging, with faster CT scanners and helical techniques CT is becoming more common. There are few data from practice in the United States regarding the age and sex distribution of patients receiving CT scans, what type of scan and how many scans they receive, or how much radiation dose CT scans contribute. We reviewed over 33,700 consecutive CT examinations done at our institution in 1998 and 1999. Information on the types of scans as well as the age and sex distribution of the patients was determined. Between 1990 and 1999, CT examinations in our institution increased from 6.1% to 11.1% of all radiology procedures. Nineteen per cent of all patients seen in our department in the last year had at least one CT scan and more than half had multiple scans on the same day. Thirty-six per cent of all patients had a prior CT examination done on an earlier date. The male/female ratio of patients was 56/44. Studies of children age 0-15 years comprised 11.2% of scans. The highest percentage of scans was done in the 36-50-year-old age group. CT scanning accounted for 67% of the effective dose from diagnostic radiology. In most large hospitals in the United States CT scanning probably accounts for more than 10% of diagnostic radiology examinations and about two-thirds of the radiation dose. Most patients have multiple scan sequences. Studies done on children are probably more common than previously thought.

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Patients infected with human immunodeficiency virus (HIV) often also have intestinal infections with Enterocytozoon bieneusi. Recently, infection with this microsporidian has been described in immunocompetent subjects, mainly from Europe. When the stools of six HIV-negative patients who presented with diarrhoea in Zimbabwe were investigated, using a recently described protocol based on PCR, two patients were found to have E. bieneusi infections. These two individuals presented with a self limited diarrhoea, abdominal cramping and nausea. These data indicate that E. bieneusi may be a more common cause of diarrhoea in Zimbabwe than previously thought. Larger, prospective studies are needed.

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OBJECTIVES: To determine the prevalence of intestinal parasites and risk factors for infection associated with diarrhea in HIV-infected patients in Harare, Zimbabwe. DESIGN: Prospective observational study. METHODS: Single stool samples were collected from 88 HIV-infected individuals presenting with diarrhea of greater than 1 week duration. Stools were examined for intestinal parasites using modified acid fast stain, fluorescence- labeled monoclonal antibody for Cryptosporidium parvum, as well as a modified trichrome stain and a PCR-based protocol for Enterocytozoon bieneusi. RESULTS: C. parvum was detected in 9% (seven out of 82) of samples evaluated, but no Cyclospora was detected. E. bieneusi was detected in 18% (10 out of 55) of stool by trichrome staining and in 51% (28 out of 55) of stool examined by PCR. Risk factors for E. bieneusi infection were: living in rural areas, consumption of nonpiped water, contact with cow dung and household contact with an individual with diarrhea. CONCLUSION: E. bieneusi infection was common in HIV-infected patients with diarrhea in Zimbabwe and may be acquired through person-to-person and fecal-oral transmission.

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OBJECTIVES: This study sought to determine the prevalence, characteristics, relation to clinical features and evolution of aortic root disease and valve disease associated with ankylosing spondylitis (AKS). BACKGROUND: Aortic root disease and valve disease are common in patients with AKS, but their clinical and prognostic implications have not been well defined. METHODS: Forty-four outpatients with AKS and 30 age- and gender-matched healthy volunteers underwent initial transesophageal echocardiography and rheumatologic evaluations. Twenty-five patients underwent clinical and echocardiographic follow-up 39+/-10 months later. RESULTS: Aortic root disease and valve disease were common in patients (82%) as compared with controls (27%; p < 0.001). Aortic root thickening, increased stiffness and dilatation were seen in 61%, 61% and 25% of patients, respectively. Valve thickening (41% for the aortic and 34% for the mitral valve) manifested predominantly (74%) as nodularities of the aortic cusps and basal thickening of the anterior mitral leaflet, forming the characteristic subaortic bump. Valve regurgitation was seen in almost half of patients, and 40% had moderate lesions. Except for the duration of AKS, aortic root disease and valve disease were unrelated to the activity, severity or therapy of AKS. During follow-up of 25 patients, in up to 24% new aortic root or valve abnormalities developed, in 12% existing valve regurgitation worsened significantly and in 20% abnormalities resolved. Twenty percent of patients developed heart failure, underwent valve replacement, had a stroke or died, as compared with 3% of control subjects. CONCLUSIONS: Aortic root disease and valve disease are common in patients with AKS, are unrelated to clinical features of AKS, can resolve or progress over time and are associated with clinically important cardiovascular morbidity.

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PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.

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Human resistance to reinfection with Schistosoma mansoni and Schistosoma haematobium correlates with elevated IgE titers against worm antigens (soluble worm antigen preparation, SWAP). In S. mansoni infection, low levels of reinfection following chemotherapy are associated with the recognition of a cloned tegumental protein Sm22.6. Because of potential species-specific differences in resistance to schistosomes, we attempted to identify Schistosoma japonicum antigens recognized by human IgE. Following a survey of 176 infected individuals in Leyte, Philippines, we show that IgE antibodies from the majority of older, high-IgE/SWAP responders recognize antigens in the 22 (Sj22)-, 45-, 78- and 97-kDa range in SWAP. Limited IgE cross-reactivity between Sj22 and Sm22 was observed following a comparison of Filipino IgE responses to these antigens. The antigen was cloned from an adult S. japonicum lambda-ZAP cDNA library (Mindoro strain) by immunoscreening with pooled high-titer IgE antisera and a rabbit anti-Sj22 polyclonal antibody. The deduced amino acid sequence of the identified cDNA clone, MJ-1, showed significant homology to Sm22.6 (74%) and Sj22.6 (99%). Although the molecular sequence of Sj22.6 has already been reported, this is the first demonstration of its recognition by human IgE, thereby strengthening its potential as a vaccine candidate. Using an overlapping peptide approach, four IgE-binding epitopes were identified in Sj22.6, two of which exhibited similarities to known IgE-binding epitopes from codfish (Gad c 1) and beta-lactoglobulin-related allergens. These findings suggest that allergy and protective immunity to helminth infection may be linked by the structural similarities of epitopes recognized by human IgE.

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A 37-year-old woman was seen for recurrent papillary carcinoma of the thyroid after thyroidectomy. After repeated surgery and I-131 therapy, follow-up I-131 scanning and thyroglobulin levels were negative. Subsequent I-131 surveillance, however, demonstrated bilateral breast uptake. A biopsy taken of this area in the right breast proved that the increased uptake was secondary to benign disease.

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Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.

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Hantavirus infection may cause diffuse air space disease, termed hantavirus pulmonary syndrome (HPS). The authors sought to determine if chest radiographs could differentiate HPS from typical acute respiratory distress syndrome (ARDS). The authors identified patients with either HPS (n = 11) or acute ARDS (n = 32) and selected the earliest chest radiograph showing diffuse airspace disease, and a chest radiograph taken 24 to 48 hours previously. Thoracic and general radiologists first viewed the chest radiograph showing diffuse air space disease, and ranked the likelihood that each case represented HPS versus ARDS. Afterward, readers viewed earlier chest radiographs and rescored each case. Receiver operating characteristic (ROC) curves from both scoring sessions were generated. The mean areas under the ROC curves for the entire group was 0.83 +/- 0.12 initially, and improved to 0.87 +/- 0.09 (p < 0.05) after viewing prior chest radiographs. Receiver operating characteristic curves of thoracic radiologists described greater areas than those of general radiologists both before and after viewing prior chest radiographs; 0.95 +/- 0.01 versus 0.78 +/- 0.08 (p < 0.05) and 96 +/- 0.02 versus 0.80 +/- 0.05 (p < 0.05). The mean sensitivity and specificity of chest radiograph interpretation for HPS was 86 +/- 13% and 74 +/- 11%, respectively. Chest radiographs can differentiate HPS from ARDS. Accuracy is improved by the use of serial radiographs and more highly trained readers. The chest radiograph findings may represent differences in the extent of alveolar epithelial damage seen in HPS and ARDS.

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PURPOSE: The authors sought to determine if the right ventricular ejection fraction (RVEF), as measured by xenon ventriculography, is depressed in patients with pulmonary emboli. The authors also sought to correlate any decrement in RVEF with the extent of lung perfusion defects. MATERIALS AND METHODS: The authors identified all patients who had lung ventilation-perfusion (V/Q) scans between January 1994 and December 1996, that were interpreted as high probability for pulmonary embolism. From these patients, the authors selected those who had undergone concurrent xenon ventriculography (XV) (n = 23), and then reprocessed the initial ventriculography data for confirmation. The authors also reviewed original V/Q scans, chest radiographs, and clinical data. A control group was drawn from patients with normal V/Q scans who had undergone XV. RESULTS: Fifteen patients (65%) with high probability V/Q scans had an abnormally low RVEF (< .32). Patients with high probability V/Q scans also had a significantly lower mean RVEF (0.28 +/- .08) than patients with normal V/Q scans (.39 +/- .08 SD). The degree of RVEF decline correlated poorly with the number of segmental perfusion defects (r = -.39). CONCLUSIONS: RVEF is often depressed in patients with high probability V/Q scans. XV can identify these patients, while routine lung V/Q scans cannot.

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Cryptosporidium parvum infection of the small epithelial intestine causes unremitting diarrhea and malabsorption that can lead to chronic and sometimes fatal illness in patients with AIDS. The illness may be ameliorated by passive oral immunoglobulin therapy. The objective of this study was to produce anti-Cryptosporidium human monoclonal antibodies for evaluation as potential therapy. All human monoclonal cell lines that produced C. parvum antibodies were originally generated from the peripheral blood lymphocytes of a human immunodeficiency virus-seronegative woman. She had recovered from C. parvum infection and had a high specific antibody titer. Hybridization of these lymphocytes with a tumor cell line was accomplished by hypo-osmolar electrofusion. Twelve clones were identified by enzyme-linked immunosorbent assay (ELISA) as secreting anti-Cryptosporidium antibodies after the initial hybridization. From the 12 positive clones, two high antibody-secreting clones, 17A and 17B, were maintained in long-term culture. A second hybridization produced two other human monoclonal cell lines, EC5 and BB2. Human monoclonal antibody from the first two cell lines bound to C. parvum sporozoites and oocysts by immunofluorescence. The ability of human monoclonal antibodies to inhibit C. parvum infection in vitro was assessed by using a human enterocyte cell line, HT29.74. The antibodies of the four different human hybridomas inhibited infection by 35 to 68% (P < 0.05) compared to a control irrelevant human monoclonal antibody derived in a similar fashion. Human monoclonal antibodies are candidate molecules for immunotherapy of C. parvum infection.

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The microsporidium Enterocytozoon bieneusi is closely linked to wasting and diarrhea in a high proportion of individuals with AIDS. However, its relative contribution to disease is uncertain because diagnosis until recently depended on procedures involving endoscopy. A sensitive PCR technique which amplifies a fragment of the small-subunit rRNA gene of E. bieneusi from formalin-fixed stool samples was developed. Of 80 formalin-fixed stool samples collected from 74 Zimbabweans and 6 U.S. patients who were human immunodeficiency virus positive, 50% tested positive for E. bieneusi by PCR, whereas 24% tested positive for E. bieneusi by light microscopy of trichrome-stained fecal smears. In addition, we describe an in situ hybridization technique which detected and identified E. bieneusi as the causative agent in all six intestinal biopsy specimens tested. Both the PCR and in situ hybridization procedures are sensitive diagnostic tools which will complement currently available techniques and enable the differentiation of E. bieneusi from other microsporidia to be made.

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A monoclonal antibody to Schistosoma japonicum which conferred significant protection against cercarial challenge in mice was produced. The predicted translation product of the cDNA corresponding to the antigen recognized by this antibody was homologous to a newly identified family of actin-binding proteins. The expressed protein bound polymerized actin and was recognized by serum from patients infected with S. japonicum.

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Schistosomiasis japonica differs significantly from Schistosoma mansoni infection in several epidemiologic, immunologic, and operational characteristics for control. Because of numerous nonhuman hosts, transmission remains high despite aggressive case finding and treatment of human cases. Diagnosis of infection using the Kato-Katz stool technique is less sensitive and specific in this than in other species of human schistosomes, making case finding and treatment a less effective approach to control. Clinically, morbidity induced by S. japonicum appears unrelated to intensity of infection, and is more severe than that of S. mansoni in terms of liver pathology and stunting of child growth and development. Both hepatic enlargement and fibrosis appear to be reversible and preventable with aggressive treatment but several operational characteristics for control of infection due to S. japonicum make the community impact of case-finding and treatment with praziquantel less pronounced than would have been predicted by the analysis of individual cases. In the Philippines, rebound morbidity following reinfection mandates short treatment intervals between screening and treatment to have a significant impact on morbidity, while in China inapparent infection (infection not diagnosed by a single stool examination) appears to be a common cause for persistent hepatic pathology. The authors conclude that for S. japonicum, mass treatment or targeted mass treatment is a more cost-effective approach than case-finding and treatment for control.

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The long-term impact of annual case-finding and chemotherapy with praziquantel on schistosomiasis japonica was examined in an 8-year longitudinal study in the Philippines. The prevalence, incidence, and intensity of infection and schistosome-induced hepatomegaly significantly decreased within 3-4 years of treatment and then stabilized despite continual population-based chemotherapy. Hepatomegaly rapidly developed in acutely infected persons, with 82% of subjects developing hepatic enlargement within 2 years of reinfection. These data suggest that abrupt discontinuation of current control measures in the Philippines may result in a rapid rebound in morbidity. Age-dependent acquired resistance to reinfection also developed in subjects chronically exposed to schistosomiasis japonica, suggesting that a vaccine may represent an alternative approach for control of this parasitic infection.

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